The Duke Center for Systems Biology (DCSB) will support research collaborations aimed at discovering, modeling, and explaining the dynamical properties of biological networks. Using high throughput techniques, biologists can now determine nearly complete lists of many of the molecular components of cells, measure relative concentrations of these components, and determine which components interact with each other. A major challenge, however, is to understand how this complex network of interactions produces the orchestrated processes characteristic of living cells and higher organisms. DCSB will approach this challenge through interdisciplinary projects involving a wide array of experimental techniques, analysis tools, and modeling methods. Each project will be a collaboration between biologists and theorists with expertise in a relevant subfield of mathematics, computer science, statistics, or physics. DCSB projects will address three broad themes: (1) cell cycle control;(2) development and differentiation;and (3) population variation. In the first two, the emphasis will be on the dynamics determined by gene regulatory networks;in the third, on evolutionary dynamics of network structure. Six initial projects have been identified for support, covering networks involved in various model systems: the yeast cell cycle, mammalian cell cycle entry, Arabidopsis root development, sea urchin embryonic development, population variation in yeast, and population variation in sea urchin. Analysis and modeling efforts will draw from expertise in Bayesian statistics, nonlinear dynamics, computational topology and geometry, and visualization. DCSB will bring together outstanding researchers as collaborators and guest scientists through sabbatical and fellowship programs and through an annual symposium on a current systems biology theme. DCSB faculty will integrate systems biology themes into several existing graduate education programs that foster vertically integrated research teams and exposure to interdisciplinary approaches to biological problems. Faculty associated with DCSB will also teach several new undergraduate systems biology courses and administer a certificate program designed both for biology students and those students in mathematical/computational majors. The results will have substantial implications for treatment of human disease through manipulation of genetic regulatory systems, as well as for fundamental biology and theories of complex systems.